1. Field of the Invention
The invention relates to the field of microfluidic devices with nonlinear responses.
2. Description of the Prior Art
Microfluidics is a technology that is establishing itself as an innovative practical tool in biological and biomedical research. Microfluidics offers the advantages of economy of reagents, small sample handling, portability, and speed. PDMS (polydimethylsiloxane) microfluidics in particular also offers industrial up-scalability, parallel fabrication, and a unique capability for complex fluid handling schemes through fluidic networks containing integrated valves and pumps.
Up to now, the configuration of such devices fell into two distinct categories, “pushup” and “pushdown” devices as shown in side cross-sectional view in FIGS. 1a and 1b depending on which direction the microvalve membranes deflected to shut off reagent flow. Both types of devices have advantages and disadvantages, which limit their usefulness in specific applications. For example, pushdown devices are used in applications where the reagents need to access the glass surface of the substrate, e.g. when chips are aligned on top of DNA or protein microarrays printed on the glass substrate. On the other hand, pushup devices allow the practical valving of significantly deeper reagent channels (˜40 μm instead of ˜10 μm), e.g. in applications involving mammalian cells. It is clear then that none of the available configurations is usable in applications demanding both deep channels and access to the glass substrate, e.g. on-chip mammalian cells expression analysis by printed microarrays. Finally, in both currently available configurations, the reagent flow is restricted to two dimensions, which severely limits the attainable device complexity.
Over the decade of its existence, PDMS (polydimethylsiloxane) microfluidics has progressed from the plain microchannel (1) through pneumatic valves and pumps to an impressive set of specialized components organized by the thousands in multilayer large-scale-integration devices. These devices have become the hydraulic elastomeric embodiment of Richard Feynman's dreams of infinitesimal machines. The now established technology has found successful application in protein crystallization, DNA sequencing, nanoliter PCR, cell sorting and cytometry, nucleic acids extraction and purification, immunoassays, cell studies, and chemical synthesis, while also sewing as the fluid handling component in emerging integrated MEMS (microelectromechanical) devices.
The prior art has developed an ingenious scheme wherein a complex system of multilayer photoresist molds, photoresist pre-masters, and PDMS masters were fabricated and then used in an involved many-step process to produce a 70 μm-thick PDMS layer with 100 μm-wide vertical cylinders connecting 70 μm-tall channels fabricated in thick PDMS slabs. The resulting three dimensional technique was successfully used in protein and cell patterning, but the challenging and labor-intensive fabrication of the devices has largely dissuaded researchers from further work along the same path.
The energetic pursuit of applications however has resulted in a premature attention shift away from fundamental microfluidics. What is needed is a fundamental technological advance that allows a simple and easy access to a large increase in the architectural complexity of microfluidic devices, as well as new possibilities for technical developments and consequent applications.